Friday, October 21, 2011

Antagonistic pleiotropy - the case for BRCA mutations

In a natural fertility population, these authors find that carriers of BRCA mutations have more children, shorter birth intervals, a later end to child-bearing, and "excess post-reproductive mortality risks".

Abstract Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.

They have a pretty lengthy and well-referenced discussion about potential mechanisms, focusing mostly on how BRCA may affect telomere length (i.e. mutations in BRCA protect telomeres) which may in turn increase fertility.

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